Multi-omics network pharmacology and experimental verification of erythropoietin in microglial neuroinflammation in neonatal hypoxic-ischemic brain injury
Preclinical study demonstrates that erythropoietin attenuates neuroinflammation and improves motor recovery in neonatal hypoxic-ischemic rats, indicating therapeutic value.
Key Points
To elucidate the neuroprotective mechanisms of erythropoietin in neonatal hypoxic-ischemic brain injury, focusing on the modulation of microglia-mediated neuroinflammation.
Screened common targets between erythropoietin and hypoxic-ischemic brain injury via databases to construct PPI networks and perform GO/KEGG pathway enrichment analyses.
Assessed core target binding affinity and stability using molecular docking and kinetic simulations.
Evaluated microglial activation, NF-κB signaling, inflammatory cytokines, neuronal apoptosis, and motor function recovery in a neonatal rat model of hypoxic-ischemic brain injury.
Identified 92 shared targets with core hub genes AKT1, STAT3, TNF, IL-6, and NFKB1 enriched in PI3K-AKT, NF-κB, and JAK-STAT pathways, exhibiting strong binding affinities from −7.4 to −9.1 kcal/mol.
EPO administration in vivo suppressed NF-κB pathway activation, reduced Iba-1+ microglia, promoted protective M2 microglial polarization, and down-regulated pro-inflammatory cytokines.
EPO treatment reduced neuronal apoptosis and led to dose-dependent improvements in motor function recovery.